crossing96/oncoscreening huggingface dataset:
A randomized prospective trial comparing Bacillus Calmette-Guérin (BCG) RIVM and Russian strains in non-muscle invasive bladder cancer: Efficacy and side effects.	BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) therapy is widely used as an adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, the optimal BCG substrain remains undetermined. This study compares the efficacy and safety of the BCG RIVM and Russian substrains in NMIBC treatment. OBJECTIVE: To evaluate recurrence-free survival (RFS), progression-free survival (PFS), and adverse event profiles between the 2 substrains. METHODS: In this randomized prospective trial, 149 patients with intermediate-, high-, and very high-risk NMIBC were randomized to receive either BCG RIVM or BCG Russian following transurethral resection of bladder tumor (TURBT). Patients with inadequate BCG therapy, short follow-up, or exposure to multiple strains were excluded from the per-protocol analysis (n = 125). Kaplan-Meier analysis was used to evaluate survival outcomes in both the per-protocol and intention-to-treat (ITT) populations. Adverse events were also assessed. RESULTS: Of 125 patients, 61 received BCG RIVM and 64 received BCG Russian. Recurrence occurred in 17 (27.9%) and 19 (29.7%) patients in the RIVM and Russian groups, respectively (P = 0.822). The 48-month RFS rates were 72.1% (CI: 60.9-83.2) and 70.3% (CI: 59.2-81.4). Progression occurred in 4 patients (6.6%) vs. 8 patients (12.5%) in the RIVM and Russian groups, respectively (P = 0.365). The 48-month PFS rates were 93.4% (CI: 87.2-99.6) and 87.5% (CI: 79.4-96.9). Kaplan-Meier curves for RFS and PFS indicated no significant difference between the 2 groups (log-rank P = 0.875 for RFS and 0.267 for PFS). Similar findings were observed in the ITT analysis (log-rank P = 0.791 for RFS and 0.419 for PFS). Adverse events were reported in 76% of patients, with no significant differences between the groups in terms of toxicity (P = 0.545). CONCLUSIONS: BCG RIVM and Russian substrains demonstrated comparable efficacy and safety, supporting substrain selection based on availability and institutional preference.	bladder
Adjuvant radiotherapy in patients with pathological high-risk bladder cancer: Acute toxicity results from a randomized multicentre phase II trial (Bladder-ART/GETUG-AFU30).	BACKGROUND AND PURPOSE: Patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy remain at significant risk of pelvic recurrence. We aim to report acute toxicity from a multicentric phase II randomized trial evaluating adjuvant radiotherapy (ART). MATERIALS AND METHODS: Patients with pathological high-risk urothelial MIBC, defined as pT3a-4b and/or pN1-2 and/or positive surgical margins, were randomized (3:1) between ART (arm A) and observation (arm B). ART consisted of IMRT (50.4 Gy / 28 fractions) to the pelvic lymph nodes ± cystectomy bed. The primary endpoint was pelvic recurrence-free survival. Herein, we report on acute toxicity (< 6 months after treatment) using the NCI CTCAE 4.0. RESULTS: From May 2018 to December 2023, 80 eligible patients from 19 centres across France were enrolled: 58 in arm A and 22 in arm B. The present safety analysis focuses on 74 patients: 52 patients in arm A who effectively initiated ART and 22 in arm B. The median age was 66 years. Chemotherapy (mostly neoadjuvant) was given in 62.2 %. All the patients in the arm A completed the treatment. The rate of grade ≥ 2 and grade ≥ 3 acute gastro-intestinal adverse events (AEs) was 28.8 % and 3.8 %, respectively in arm A, and 4.5 % and 0 % respectively in arm B. Of the two grade ≥ 3 GI AE observed in arm A, one was attributed to surgical complications and the other to disease progression. The rate of grade ≥ 2 and grade ≥ 3 acute urinary AEs was 5.8 % and 0 %, respectively in arm A, and 9.1 % and 4.5 % respectively in arm B. As exploratory analyses, when focusing on AE of grade ≥ 2, these proportions were greater for Arm A (28.8 % [n = 15] vs. 4.5 % [n = 1]; p = 0.028, Fisher's exact test). Overall, no radiotherapy-related grade ≥ 3 AE was observed. CONCLUSION: From a randomized multicentric phase II trial, despite a logical higher rate of radiotherapy-related AE in the experimental arm, low rates of moderate to severe acute toxicity suggest the safety of ART for pathological high-risk MIBC. Efficacy end-points results are awaited.	bladder
Qualitative Interferon-γ Release Assay for Predicting Response to BCG Instillations in Bladder Cancer.	BACKGROUND: This study aims to investigate the potential use of qualitative interferon-γ release assay, specifically T-spot testing focusing on culture filtrate protein 10 (CFP-10) positivity, in predicting the response of patients with high-risk non-muscle invasive bladder cancer (NMIBC) to intracavitary Bacillus Calmette-Guerin (BCG) vaccine instillation. METHODS: Patients diagnosed with high-risk NMIBC were retrospectively identified from an institutional database and subsequently underwent prospective T-spot testing. Following the completion of an adequate course of BCG instillation, patients who were unresponsive to BCG were assigned to the study group. By contrast, those who remained recurrence free for at least one year post-treatment were assigned to the control group. RESULTS: In this cohort of 42 patients with high-risk NMIBC, the median age was 67, and 40.0% were unresponsive to BCG. The distribution comprised 50.0% pTa and 81% high-grade cases. Over a median follow-up of 18 months, the positive BCG response varied between pTa (81%) and pT1 (38%; p = 0.005), and T-spot testing revealed positivity in 75.0% of the control group and 92% in BCG-unresponsive patients (p = 0.235). Notably, CFP-10 positivity was significantly more prevalent in the BCG-unresponsive group, observed in 91.7% of the patients, in contrast to 35.7% in the control group (p = 0.004). CONCLUSIONS: T-spot test or more specifically CFP-10 positivity is a potential marker for predicting response to BCG instillation in patients with NMIBC.	bladder
Integration of Single-cell and bulk RNA sequencing data uncovers lymphatic metastasis-related prognostic genes and a predictive model in bladder cancer.	Bladder cancer (BLCA) exhibits considerable heterogeneity, and research into its tumor microenvironment and prognostic biomarkers remains insufficient. This study aims to identify key prognostic genes and immune microenvironment factors to enhance clinical assessment. Primary tumor (PT) and lymph node metastasis (LNM) samples were obtained from patients with BLCA, and single-cell RNA sequencing (scRNA-seq) was conducted to analyze cellular composition and functional variations. Prognostic genes were identified based on integrated bulk transcriptomic data, leading to the development of a risk model. Functional enrichment analyses further elucidated the molecular characteristics of high- and low-risk cohorts. The scRNA-seq analysis revealed significantly elevated metabolic activity in epithelial cells of LNM. A subpopulation of epithelial cells, defined by 133 characteristic genes, was identified as pivotal in the lymphatic metastasis of BLCA. The prognostic model, derived from nine key genes (APOL1, CAST, DSTN, SPINK1, JUN, S100A10, SPTBN1, HES1, and CD2AP), demonstrated robust predictive performance. Functional enrichment analysis indicated that the high-risk group predominantly activated extracellular matrix (ECM) receptor interactions and the complement pathway, while the low-risk group was primarily associated with carbohydrate metabolism pathways. This study provides insights into the tumor heterogeneity and immune microenvironment of BLCA, introduces a high-precision prognostic model, and establishes a novel theoretical basis for personalized BLCA treatment.	bladder
[Association between HER2 overexpression and recurrence rate in patients with non-muscle-invasive bladder cancer following anthracycline-based intravesical instillation therapy].	Objective: To assess the clinicopathological characteristics of non-muscle-invasive bladder cancers (NMIBC) with high expression of human epidermal growth factor receptor 2 (HER2) and to examine the prognostic values of HER2 expression in NMIBC patients with intravesical anthracycline instillation. Methods: A total of 221 NMIBC samples diagnosed between January 1, 2017 and April 15, 2024 were collected. Their clinical, diagnostic and treatment features were analyzed. The expression of HER2 protein and the Ki-67 proliferation index were assessed using immunohistochemistry (IHC). For the patients with HER2 high-expression (IHC 3+), the clinical pathological features (age, gender, tumor grade, Ki-67 expression level, tumor size, and tumor number) were compared with those without (i.e., HER2 IHC 0/1+/2+). The impact of HER2 expression on the recurrence-free survival (RFS) of patients with intravesical anthracycline (epirubicin or pirarubicin) instillation after transurethral resection of bladder tumor (TURBT) was evaluated. Results: Among the 221 NMIBC patients, 30 (13.6%) were HER2 IHC 3+, 142 (64.3%) HER 2+, 46 (20.8%) HER2 1+, and 3 (1.4%) HER2 IHC 0. The proportion of high-grade tumors in patients with HER2 high-expression was higher than that in patients without (83.3% versus 44.5%, P<0.001). Additionally, a high Ki-67 index (≥20%) was more commonly noted in HER2 high-expression tumors (P=0.003). In the patients treated with intravesical anthracycline instillation, HER2 high-expression was associated with a shorter RFS (P<0.001). Conclusion: HER2 high-expression seems to be not only associated with worse clinicopathological features of NMIBC but also a poor RFS in NMIBC patients treated with anthracycline instillation after TURBT.	bladder
The Effect of Chronic Liver Disease on Adverse In-Hospital Outcomes After Radical Cystectomy and Ileal Conduit Urinary Diversion.	BACKGROUND: Radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (BCa). Chronic liver disease (CLD) may predispose to worse in-hospital outcomes after RC and ileal conduit, but this association has not been investigated. The current study addressed this knowledge gap. METHODS: Descriptive analyses, propensity score-matching (PSM), and multivariable logistic and Poisson regression models were used to address BCa patients in the National Inpatient Sample treated with RC and ileal conduit (2006-2019). RESULTS: Of 15,104 RC and ileal conduit patients, 241 (1.6 %) had CLD at baseline. Compared with their non-CLD counterparts, the CLD patients exhibited significantly higher rates of adverse in-hospital outcomes in 9 of 13 categories, namely, acute kidney injury (AKI, Δ+12.0 %), overall complications (Δ+11.0 %), pulmonary complications (Δ+9.0 %), blood transfusions (Δ+8.0 %), prolonged hospital stay (Δ+7.0 %), infectious complications (Δ+7.0 %), critical care therapies (Δ+4.0 %), in-hospital mortality (Δ+3.6 %), and total hospital charges (THC, Δ+18, 042 US$) (all p < 0.05). After multivariable adjustment, CLD independently predicted higher rates of adverse in-hospital outcomes in the same categories, namely, in-hospital mortality (odds ratio [OR], 2.7; 95 % confidence interval [CI], 1.3-4.9), infectious complications (OR, 2.5; 95 % CI 1.6-3.8), AKI (OR, 2.1; 95 % CI 1.6-2.9), pulmonary complications (OR, 2.0; 95 % CI 1.4-2.8), overall complications (OR, 1.9; 95 % CI 1.7-2.9), critical care therapies (OR, 1.6; 95 % CI 1.2-1.9), blood transfusions (OR, 1.4; 95 % CI 1.1-1.9), prolonged hospital stay (OR, 1.4; 95 % CI 1.1-1.8), and THC (OR, 1.2; 95 % CI 1.1-1.4) (all p < 0.05). CONCLUSIONS: Although CLD appears to predispose to higher rates of adverse in-hospital outcomes after RC and ileal conduit, it does not increase the rates of these outcomes in a prohibitive fashion.	bladder
Intravesical BCG for bladder cancer treatment complicated by disseminated BCG (BCGosis) with pericardial effusion and tamponade.	Intravesical BCG instillations are first-line adjuvant treatment for non-muscle invasive bladder cancer. Infectious complications are typically limited to the genitourinary system but can infrequently affect distant organs due to haematogenous spread. We describe the case of an elderly man who presented with several months of malaise and hypotension and was diagnosed with disseminated BCG (BCGosis) with endocarditis and pericardial effusion resulting in cardiac tamponade. This case illustrates the potentially insidious presentation of BCGosis and challenges in diagnosis, highlighting the need for vigilance among clinicians treating these patients.	bladder
An Anoikis-Based Prognostic Signature Identifies MYC as a Key Regulator of Malignancy and Immunotherapy Resistance in Bladder Cancer.	BACKGROUND: Resistance to anoikis is a critical mechanism that enables metastatic dissemination. Abrogation of this cellular safeguard is therefore a hallmark of aggressive cancer progression. Despite the importance of anoikis, there are still few biomarkers among anoikis-related genes (ARGs) that could aid in the prognostication of bladder cancer (BC) patients and potentially serve as drug targets. METHODS: This study leveraged bioinformatics analyses of publicly available BC datasets to evaluate the association between differentially expressed ARGs and patient prognosis. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was employed to build a novel prognostic signature model for BC based on ARGs. This model was also used to predict the response of BC to anticancer drugs. Additionally, immunohistochemistry was used to assess expression of the key gene, MYC, in BC samples obtained from patients undergoing surgery and from those receiving immune checkpoint inhibitor (ICI) therapy. RESULTS: The ARG-based signature, developed and validated through the analysis of public databases, was an independent predictor of patient outcomes. Furthermore, it effectively stratified patients into two cohorts (high- and low-risk), allowing investigation of differential drug sensitivities. The risk stratification model identified 10 ARGs (IGF1, CALR, E2F1, MYC, PLK1, SATB1, FASN, ID2, RAC3, and GKN1) as potential therapeutic vulnerabilities. Notably, MYC was identified as a central hub gene within the ARG signature. Elevated MYC expression was strongly associated with worse prognosis in muscle-invasive bladder cancer (MIBC), and with a diminished response to immunotherapy. CONCLUSION: This work demonstrated significant prognostic value for the ARG-based model. Specific ARGs could function as crucial biomarkers for patient outcome, while simultaneously offering new avenues for therapeutic intervention.	bladder
Investigation on the current status of secondary transurethral resection for bladder cancer among Chinese urologists and construction of an acceptance prediction model.	OBJECTIVE: Through the investigation of the current situation of bladder cancer secondary electrotomy performed by urologists in China, it provides reference for further improvement and improvement of diagnosis and treatment norms. METHODS: From September 3, 2023 to October 7, 2023, questionnaires compiled by researchers were distributed and collected from urologists across the country in the form of electronic questionnaires through the questionnaire Star platform; The questionnaire data were exported online using SPSS 26.0 software (SPSS Inc, Chicago, IL, USA) and R language (R Foundation for Statistical Computing, Vienna, Austria, Austria). Version 4.2.1) for data analysis. Count data were described by percentages, and comparisons between groups were made by chi-square test or Fisher's exact test. Logistic regression was used to screen out the influencing factors related to the status of secondary electrotomy for bladder cancer performed by Chinese urologists and to construct a predictive model for the column-line diagram. ROC curves, calibration curves, and DCA curves were plotted to evaluate the model and validate its efficacy. RESULTS: A total of 514 valid questionnaires were returned. 77.2% (397/514) of the physicians interviewed were from tertiary care hospitals. 21.2% (109/514) were from secondary care hospitals. The acceptance rate of secondary electrosurgical resection of bladder cancer among Chinese urologists was 87.74%, with 12.26% still opposed to the procedure.The majority of respondents believed that secondary electroresection could be performed if the indications recommended by the guidelines were met (75%), while a significant number felt that the initial electroresection was complete and did not require a second (37.74%), or they decided whether to perform a secondary electroresection based on their clinical experience (40.27%). CONCLUSION: Survey results indicate that secondary transurethral resection enhances staging accuracy, eliminates residual lesions, and decreases recurrence and progression rates. However, it serves as a means to compensate for shortcomings in the initial resection. Advances in NMIBC treatment techniques assist in reducing or avoiding the need for secondary transurethral resection in bladder cancer cases. This study is the first to develop a predictive model for Chinese urologists' acceptance of secondary transurethral resection for bladder cancer and analyzes their perspectives on the procedure, offering a reference for future research.	bladder
Unlocking the role of prostate transmembrane androgen inducible protein 1 in gemcitabine resistance: modulation of P38-mitogen-activated protein kinase/C-C motif chemokine ligand 2 and M2 macrophage polarization in bladder cancer.	Bladder cancer (BLCA) is a highly aggressive malignancy, with chemotherapy resistance being a significant factor in treatment failure. In the tumor microenvironment, M2 macrophage polarization is essential for immune suppression and treatment resistance. Key genes linked to M2 macrophage polarization and gemcitabine resistance in BLCA are examined in this work, along with possible underlying processes. Bioinformatics analyses were performed to identify differentially expressed genes in BLCA. Key hub genes related to M2 macrophage polarization and gemcitabine resistance were identified using various bioinformatics tools, including Cibersort, weighted gene coexpression network analysis, and gene set enrichment analysis. The effects of prostate transmembrane androgen inducible protein 1 (PMEPA1) silencing on cell viability, gemcitabine resistance, and macrophage polarization were further assessed using reverse transcription-quantitative PCR, Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ELISA, and flow cytometry. Bioinformatics analysis revealed that PMEPA1 is a core gene associated with M2 macrophage polarization and gemcitabine resistance. Knockdown of PMEPA1 in BLCA cell lines reduced cell viability and enhanced gemcitabine sensitivity. Silencing of PMEPA1 also promoted M1 macrophage polarization while decreasing M2 macrophage polarization, as shown by the downregulation of cluster of differentiation (CD) 163 + and upregulation of CD86 + . Mechanistically, PMEPA1 regulated the P38-mitogen-activated protein kinase (MAPK)/C-C motif chemokine ligand 2 (CCL2) axis, leading to M2 macrophage polarization. Our findings suggest that PMEPA1 plays a crucial role in regulating M2 macrophage polarization and gemcitabine resistance in BLCA by activating the P38-MAPK/CCL2 signaling pathway.	bladder
Histone deacetylase HDAC7 restricts CD8 + T cell tumor infiltration and limits immunotherapy sensitivity in bladder cancer: reversal by pinocembrin.	BACKGROUND: The limited response rate and substantial interindividual variability in immunotherapy outcomes remain major barriers to improving prognosis in patients with bladder cancer (BCa). As central effectors of antitumor immunity, the extent of CD8 + T cell infiltration into tumors is a key determinant of immunotherapy response. Members of the histone deacetylase (HDAC) family play critical roles in modulating tumor immune evasion and sensitivity to immunotherapy, making HDAC inhibitors of clinical interest. METHODS: A retrospective analysis was performed using data from the IMvigor210 clinical trial and follow-up data from patients with locally advanced BCa who received adjuvant immunotherapy at our center, assessing the association between HDAC1-11 expression and immunotherapy response. RNA sequencing, gene set enrichment analysis (GSEA), chromatin immunoprecipitation PCR (ChIP-PCR), co-immunoprecipitation (Co-IP), mass spectrometry, lysine site mutagenesis, RNA immunoprecipitation, and bioinformatics analysis were employed to outline the HDAC7-BTRC-SRSF7-CCL5 pathway. The immunoregulatory function of HDAC7 was evaluated using CD8 + T cell co-culture assays and tumor models in humanized NOG (HuNOG) mice. Virtual screening, MicroScale Thermophoresis (MST), and HDAC activity assays were conducted to identify potential HDAC7 specific inhibitor. The immunosensitizing effect of Pinocembrin on BCa immunotherapy was validated using a C57BL/6 mouse tumor-bearing model. RESULTS: Among the HDAC family members, only HDAC7 expression was significantly associated with immunotherapy response. HDAC7 was overexpressed in BCa and correlated with poorer prognosis. Functional assays demonstrated that HDAC7 suppresses CD8 + T cell infiltration, thereby reducing sensitivity to PD-1 antibody treatment. Mechanistically, HDAC7 reduced acetylation at lysine 24 of the splicing regulator SRSF7, enhancing BTRC-mediated ubiquitination and degradation of SRSF7, which promoted the processing and expression of CCL5 mRNA-a chemokine essential for CD8 + T cell recruitment. Furthermore, Pinocembrin was identified as a selective HDAC7 inhibitor that restores CD8 + T cell infiltration and improves immunotherapy efficacy in BCa. CONCLUSIONS: HDAC7 represents a promising diagnostic and therapeutic target in BCa immunotherapy. Pinocembrin, as a specific HDAC7 inhibitor, holds potential as a combination therapy agent to improve immunotherapy response in BCa.	bladder
Analysis of the Fragmentation and Integrity of Urine Cell-Free DNA as a Diagnostic and Staging Biomarker for Bladder Cancer.	Bladder cancer (BC) is a lethal urological malignancy, with current diagnostic and follow-up methods being invasive and costly. Cell-free DNA (cfDNA) in liquid biopsies has shown promise in cancer diagnostics, but its fragmentation and integrity in urine remain underexplored in BC, becoming the aim of this study. cfDNA was isolated from the urine of 156 patients with BC of most stages and 79 matched controls without renal or bladder conditions. The amount of a large (>250-bp) and a nested small (<125-bp) fragment of ACTB, AR, MYC, BCAS1, and STOX1 was quantified by quantitative real-time PCR. Fragmentation and integrity (ratio of large/small) were analyzed with ordinal logistic regression. The increase in the ratio of large/small ACTB fragments and the small fragments of AR and MYC may represent a valuable tool to diagnose and stage BC when classified as both non-muscle-invasive and muscle-invasive BC or considering grades and stages separately. The small fragment of MYC, leading the effect observed, displayed a valuable diagnostic capacity [area under the receiver operating characteristic (ROC) curve = 0.7221; 95% CI, 0.6527-0.7915; P < 0.0001; sensitivity = 50%; specificity = 95%], particularly for muscle-invasive BC (area under the ROC curve = 0.8098; 95% CI, 0.6674-0.9523; P < 0.0001; sensitivity = 70%; specificity = 97%). Herein, the analysis of urine cfDNA fragmentation and integrity of these surrogate markers is proposed as noninvasive biomarkers to diagnose and stage BC. Once validated, the proposed biomarkers could improve patient management by reinforcing or substituting current invasive and expensive techniques.	bladder